Abstract
BackgroundThe role played by the humoral immune response in animals vaccinated against a mycobacterial disease such as paratuberculosis, is not well understood. Sheep vaccinated against Mycobacterium avium subsp. paratuberculosis (MAP) can still become infected and in some cases succumb to clinical disease. The strength and location of the humoral immune response following vaccination could contribute to the ability of sheep to clear MAP infection. We examined the peripheral antibody response along with the localised humoral response at the site of paratuberculosis infection, the ileum, to better understand how this contributes to MAP infection of sheep following vaccination and exposure.ResultsThrough assessing MAP specific serum IgG1 and IgG levels we show that the timing and strength of the humoral immune response directly relates to prevention of infection following vaccination. Vaccinated sheep that subsequently became infected had significantly reduced levels of MAP specific serum IgG1 early after vaccination. In contrast, vaccinated sheep that did not subsequently become infected had significantly elevated MAP specific serum IgG1 following vaccination. Furthermore, at 12 months post MAP exposure, vaccinated and subsequently uninfected sheep had downregulated expression of genes related to the humoral response in contrast to vaccinated infected sheep where expression levels were upregulated.ConclusionsThe timing and strength of the humoral immune response following vaccination against paratuberculosis in sheep directly relates to subsequent infection status. An initial strong IgG1 response following vaccination was crucial to prevent infection. Additionally, vaccinated uninfected sheep were able to modulate that response following apparent MAP clearance, unlike vaccinated infected animals where there was apparent dysregulation of the humoral response, which is associated with progression to clinical disease.
Highlights
The role played by the humoral immune response in animals vaccinated against a mycobacterial disease such as paratuberculosis, is not well understood
Humoral immunity is believed to play a role in the protective response against intracellular mycobacterial pathogens, such as Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of paratuberculosis in ruminants [1, 2]
Most work on correlates of vaccine-induced protection against paratuberculosis has focused on the cell mediated immune (CMI) response, recent studies have suggested a role for B cells as well [16, 17]
Summary
The role played by the humoral immune response in animals vaccinated against a mycobacterial disease such as paratuberculosis, is not well understood. The strength and location of the humoral immune response following vaccination could contribute to the ability of sheep to clear MAP infection. We examined the peripheral antibody response along with the localised humoral response at the site of paratuberculosis infection, the ileum, to better understand how this contributes to MAP infection of sheep following vaccination and exposure. Humoral immunity is believed to play a role in the protective response against intracellular mycobacterial pathogens, such as Mycobacterium avium subsp. There is a need to explore alternate or additional markers of vaccine protection to truly understand a protective vaccine response To this point, most work on correlates of vaccine-induced protection against paratuberculosis has focused on the CMI response, recent studies have suggested a role for B cells as well [16, 17]
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